The protective role of innate lymphoid cells (ILC) after hematopoietic stem cell transplantation. (LSBR 1438) FELLOWSHIP )

Project leader: Dr. Mette D. Hazenberg (AMC)
Postdoc: Dr. Vera van Hoeven (March 2015 – Sept. 2020 (80%)
Technician: Nienke Haverkate (July 2017 – July 2019)

Transplantation of healthy donor stem cells is often needed to cure patients with malignant hematologic diseases such as acute leukemia or lymphoma. While such transplantation is very effective, it can also be very dangerous. With the transplantation of stem cells, the immune system of the patient will be replaced by a new immune system, from the stem cell donor. As this donor immune system is new to the patient, it will tend to ‘see’ the patient’s healthy organs as foreign. If this happens, a disease can develop called ‘graft versus host disease’. Graft versus host disease can be very aggressive, in particular when unresponsive to corticosteroids, such as prednisolone. Every year, 10-30% of patients that were treated with donor stem cell transplantation succumb to graft versus host disease and related complications.
Graft versus host disease is often provoked by damage to tissues. Tissue damage is caused for example by chemotherapy and radiotherapy that patients receive prior to the transplantation. In the project we have investigated a certain family of immune cells that help prevent tissue damage and help damaged tissues to recover. These cells are called ‘innate lymphoid cells’ or ILC. We found that ILC not only protect against tissue damage, they also prevent other immune cells to mount inflammatory responses. When patients received a donor cell transplant with ample amounts of ILC, they did not develop graft versus host disease. This was in contrast to patients who received a donor cell transplant with low numbers of ILC. Based on the findings of the present project we are now investigating whether we can use ILC as a cellular therapy to prevent graft versus host disease in donor cell transplantation patients.